Impaired serine metabolism complements LRRK2-G2019S pathogenicity in PD patients

Parkinson's disease (PD) is a multifactorial disorder with complex etiology. The most prevalent PD associated mutation, LRRK2-G2019S is linked to familial and sporadic cases. Based on the multitude of genetic predispositions in PD and the incomplete penetrance of LRRK2-G2019S, we hypothesize that modifiers in the patients' genetic background act as susceptibility factors for developing PD. To assess LRRK2-G2019S modifiers, we used human induced pluripotent stem cell-derived neuroepithelial stem cells (NESCs). Isogenic controls distinguish between LRRK2-G2019S dependent and independent cellular phenotypes. LRRK2-G2019S patient and healthy mutagenized lines showed altered NESC self-renewal and viability, as well as impaired serine metabolism. In patient cells, phenotypes were only partly LRRK2-G2019S dependent, suggesting a significant contribution of the genetic background. In this context we identified the gene serine racemase (SRR) as a novel patient-specific, developmental, genetic modifier contributing to the aberrant phenotypes. Its enzymatic product, n-serine, rescued altered cellular phenotypes. Susceptibility factors in the genetic background, such as SRR, could be new targets for early PD diagnosis and treatment.Analytical BioScience

Psychosocial risk markers for new onset irritable bowel syndrome - results of a large prospective population-based study

Irritable bowel syndrome (IBS) affects up to 22% of the general population. Its aetiology remains unclear. Previously reported cross-sectional associations with psychological distress and depression are not fully understood. We hypothesised that psychosocial factors, particularly those associated with somatisation, would act as risk markers for the onset of IBS. We conducted a community-based prospective study of subjects, aged 25–65 years, randomly selected from the registers of three primary care practices. Responses to a detailed questionnaire allowed subjects’ IBS status to be classified using a modified version of the Rome II criteria. The questionnaire also included validated psychosocial instruments. Subjects free of IBS at baseline and eligible for follow-up 15 months later formed the cohort for this analysis (n = 3732). An adjusted participation rate of 71% (n = 2456) was achieved at follow-up. 3.5% (n = 86) of subjects developed IBS. After adjustment for age, gender and baseline abdominal pain status, high levels of illness behaviour (odds ratio (OR) = 5.2; 95% confidence interval (95% CI) 2.5–11.0), anxiety (OR = 2.0; 95% CI 0.98–4.1), sleep problems (OR = 1.6; 95% CI 0.8–3.2), and somatic symptoms (OR = 1.6; 95% CI 0.8–2.9) were found to be independent predictors of IBS onset. This study has demonstrated that psychosocial factors indicative of the process of somatisation are independent risk markers for the development of IBS in a group of subjects previously free of IBS. Similar relationships are observed in other “functional” disorders, further supporting the hypothesis that they have similar aetiologies

The Role of Dietary Approach in Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a chronic functional disorder of the gastrointestinal tract and is one of the most frequent gastrointestinal diseases. In IBS multiple pathophysiological mechanisms including alterations in intestinal motility, permeability, nutrient absorption, and intestinal microbiota have been implicated. Foods are commonly reported by patients to be a trigger of symptoms and therefore are likely involved in the generation of symptoms in IBS. Among all possible therapeutic options, a first-line approach to IBS is dietary education and identification of foods potentially responsible for the onset or worsening of symptoms. Dietary approaches include reduction of gas-producing foods (i.e. fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs)), lactose and gluten. Further studies are required to link the ultimate role of diets in different IBS subtypes

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Not AvailableSustaining soil and land quality under intensive land use and fast economic development is a major challenge for improving crop productivity in the developing world. Assessment of soil and land quality indicators is necessary to evaluate the degradation status and changing trends of different land use and management interventions. During the last four decades, the Indo-Gangetic Plains (IGP) which covers an area of about 52.01 m ha has been the major food producing region of the country. However at present, the yield of crops in IGP has stagnated; one of the major reasons being deterioration of soil and land quality. The present article deals with the estimation of soil and land quality indicators of IGP, so that, proper soil and land management measures can be taken up to restore and improve the soil health. Use of principal component analysis is detailed to derive the minimum dataset or indicators for soil quality. The article also describes spatial distribution of soil and land quality with respect to major crops of IGP.Not Availabl

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